ABSTRACT
Objective:To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） in MKR mice. Method:Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group，original Yinchenhao Tang （17.16 g·kg<sup>-1</sup>） group，Yinchenhao Tang group at a specified dose （4.68 g·kg<sup>-1</sup>） in teaching materials，and positive drug ［metformin + simvastatin， （65+2.6）×10<sup>-3</sup> g·kg<sup>-1</sup>］ group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group，the liver wet weight，oral glucose tolerance test （OGTT），serum inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>），and changes in blood lipid and liver function were determined. Hematoxylin-eosin （HE） staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope，followed by the detection of Toll-like receptor 4 （TLR4），myeloid differentiation factor 88 （MyD88），and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） protein expression by Western blot. Result:Compared with the model group，the medication groups exhibited significantly reduced liver wet weight index （<italic>P</italic><0.01），improved OGTT result （<italic>P</italic><0.05），and down-regulated serum IL-6 and TNF-<italic>α</italic> levels （<italic>P</italic><0.01）. In terms of morphological changes，Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover， Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4，MyD88，and NF-<italic>κ</italic>B in liver tissue of MKR mice with T2DM combined with NAFLD （<italic>P</italic><0.05），and the down-regulation of TLR4 and NF-<italic>κ</italic>B in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials （<italic>P</italic><0.05）. Conclusion:Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4，MyD88，and NF-<italic>κ</italic>B expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.
ABSTRACT
Annexin A1 (ANXA1) is dysregulated in the various tumors. However, the role and mechanism of ANXA1 in the cancers are poorly understood. In this study, we first showed a clinically positive correlation between ANXA1 and autophagy-associated protein SQSTM1 expression in nasopharyngeal carcinoma (NPC) and ANXA1-regulating SQSTM1 expression through autophagy, and further demonstrated that ANXA1 inhibited BECN1 and ATG5-dependent autophagy in the NPC cells. Using phospho-kinase antibody array to identify signaling through which ANXA1 regulated NPC cell autophagy, we found that ANXA1-suppressed autophagy was associated with PI3K/AKT signaling activation. We also showed that ANXA1 expression was significantly increased in the NPCs with metastasis relative to NPCs without metastasis and positively correlated with lymphonode and distant metastasis; high ANXA1 expression in the NPC cells promoted in vitro tumor cell migration and invasion and in vivo metastasis. Lastly, we showed that inhibition of autophagy restored the ability of tumor cell migration and invasion, epithelial-mesenchymal transition (EMT)-like alterations and in vivo metastasis in the ANXA1 knockdown NPC cells with autophagy activation; ANXA1-suppresed autophagy induced EMT-like alterations possibly by inhibiting autophagy-mediated degradation of Snail. Our data suggest that ANXA1-suppressed autophagy promotes NPC cell migration, invasion and metastasis by activating PI3K/AKT signaling pathway, highlighting that the activation of autophagy may inhibit metastasis of NPC with high ANXA1 expression.
